It is proposed to investigate the cellular and subcellular events that result from antigen and mitogen activation of thymus-derived lymphocytes (T cells). In vivo and in vitro activation of T cells will be studied in an attempt to determine the requirements for this activation. The involvement of other cell types, such as the macrophage, or cell products can be evaluated. Studies will be performed to investigate the development of the activated T cell and the duration of the activated state. The activation of T cells from the spleen and lymph nodes of immunized mice will be investigated, and the development of "helper" or "suppressor" activity effecting B cells in in vitro immune responses will be compared. In addition, the effect of various antigen doses on activation and the maintenance of activated or "memory" T cells will be studied. The T cell has to undergo some form of differentiation or development in order to become specifically activated, and the sensitivity of this developmental process to x-irradiation, antimetabolites, and inhibitors of DNA, RNA, and protein synthesis will be examined. The physiological T cell changes which result from antigen activation and development into "memory" t cells may be due to quantitative or qualitative changes. In order to determine what kind of changes do occur, some biophysical and biochemical characteristics of unprimed and specifically activated T cells will be compared. Information obtained by comparing normal and activated T cells will be used to investigate the mechanisms of T cell regulation of B cells for the production of specific antibodies. Since T and B cells may directly interact, changes of the T cell's plasma membrane as a result of antigen activation may be of interest; therefore, the membrane's glycoprotein content and enzymatic activity will be investigated. Specific emphasis will be given to quantitative and qualitative changes in membrane protein markers such as Thy 1, Ly 1,2,3, and 5, Ia, etc. In addition, the ability of T cell membrane fractions and certain membrane-found enzymes to stimulate B cells will be determined.